tbuckley/cabot-search huggingface dataset:
Safety and efficacy of SHR-1316 combined with chemotherapy and sequential chest radiotherapy as first-line therapy for extensive-stage small cell lung cancer (ES-SCLC): The results from a phase II single-arm trial.
Authors: Dawei Chen, Bing Zou, Xiangjiao Meng, Wei Huang, Qian Shao, Xiaoyong Tang, Jun Guo, Xudong Hu, Yan Zhang, Lei Fu, Yuan Jiajia, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2022)

8563 Background: Impower133 and CASPIAN studies showed that PD-L1 antibody combined with first-line chemotherapy could prolong the overall survival. Previous studies have shown that radiotherapy could potentially promote tumor antigen presentation and reverse immunosuppressive microenvironment in tumor. The purpose of this study was to explore the efficacy and safety of SHR-1316 (PD-L1 antibody) combined with chemotherapy and sequential chest radiotherapy as first-line therapy for ES-SCLC. Methods: Key inclusion factors were 18-75 years old, histologically or cytologically confirmed ES-SCLC, ECOG performance status 0-1, no previous systematic treatment. Patients (pts) included in this study received 4̃6 cycles of SHR-1316 (20mg/kg, D1, q3w) combined with EP/EC (cisplatin 75mg/m² D1-3 q3w or carboplatin AUC = 5, D1 q3w; etoposide 100mg/m 2 , D1-5, q3w), sequentially SHR-1316 combined with chest radiotherapy (≥3Gy*10f or ≥2Gy*25f, involved- field irradiation), and then entered the maintenance treatment stage until disease progression or intolerable side effects. The main endpoints included PFS, ORR and safety. Results: From October 2020 to December 2021, 31 pts with ES-SCLC received at least one dose of SHR-1316. The median age was 64 (range: 37-75) with 25(80.6%) male, 22(71%) former smokers and 31 (100%) ECOG performance status 1. 17 (54.8%) pts were with brain metastasis, 8 (25.8%) pts with liver metastasis, 8 (25.8%) pts with kidney/adrenal metastasis, 7(22.6%) pts with bone metastasis. At the data cutoff date, 15 pts remained on treatment, the average number of treatment cycles was 5.19. 24 pts had at least one 1 post-treatment tumor assessment. The median PFS was 7.56 months, the confirmed ORR and DCR in all pts were 50% (12/24) and 87.5% (21/24), respectively. The confirmed ORR and DCR in pts with brain metastasis were 38.5% (5/13) and 76.9% (10/13), and were 63.6% (7/11) and 100% (11/11) in pts without brain metastasis. In pts received chest radiotherapy, the confirmed ORR and DCR were 80% (8/10) and 100% (10/10). During the study period, 23 (74.2%) pts had adverse drug reactions, and 16 (51.6%) pts had grade 3 or 4 adverse drug reactions, including 12 (38.7%) neutropenia 8 (25.8%) leukopenia, 2 (6.5%) thrombocytopenia, 2 (6.5%) anemia, 1(3.2%) lymphocytopenia, 1(3.2%) amylase increased. No grade 5 adverse drug reaction was observed. Conclusions: SHR-1316 combined with chemotherapy and sequential chest radiotherapy as first-line therapy for ES-SCLC showed promising efficacy and acceptable safety. It is worthy of further clinical exploration. Clinical trial information: NCT04562337.
Analysis of genomic alterations in pan-cancer from a large real-world Chinese population.
Authors: Zhouhuan Dong, Jie Gao, Fengwei Zhu, Fei Gai, Wenqing Su, Zhixin Liang, Xiaodong Tian, Huaiyin Shi
Journal: Journal of Clinical Oncology (2022)

10568 Background: Effective targeted therapy sorely depends on comprehensive and precise genomic profiling. Besides, single nucleotide variations (SNVs) and InDels, gene fusions, as drivers and therapeutic targets of great importance, are not yet well characterized in Chinese patients. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumor tissues from 1,384 pan-cancer patients were collected and sequenced using next-generation sequencing (NGS) targeting 40 cancer genes including SNV, fusion and assessing copy number variation (CNV) (AmoyDx HANDLE Classic Panel). qPCR and fluorescence in situ hybridization (FISH) were further applied to verify NGS detected fusion genes. Results: 1,384 patients were recruited including 890 lung cancers, 272 colorectal cancers, 174 gastric cancers, and 48 endometrial cancers. The prevalence of fusion genes (5.49%), including ALK-fusion (2.67%), ROS1-fusion (0.94%), RET-fusion (0.72%), NRG1-fusion (0.29%), and NTRK-fusion (0.07%), was nearly double the frequency of previously reported data from East Asians. Prevalence of fusion genes varied in different types of cancers. For instance, ALK (3.7%), ROS1 (1.5%), RET (1.0%) and NRG1 (0.2%) fusions were largely found in patients with non-small cell lung cancer (NSCLC), and were rarely detected in other cancer types. Further analysis of genomic alterations in fusion-positive patients revealed that, TP53 (21%) was the most frequently co-occurred mutated gene with ALK fusion, while RET fusions and ROS1 fusions were rarely accompanied by other mutated genes. In addition, two patients with RBPMS- NRG1 fusion were accompanied by BRAF and RB1 mutations, whereas no co-occurred mutation was found in patients with other partners of NRG1. Patients with inconsistent results of RNA-based NGS and FISH validation fusions are still being followed for treatment and survival, updated data will be available at the time of the presentation. Conclusions: Genomic alterations in real-world Chinese populations have specific characteristics, especially fusion genes. Further characterization of these variants is essential for clinics to guide appropriate targeted therapies.
Risk factors and clinical characteristics of pneumonitis among patients with ALK-rearranged non-small cell lung cancer who received alectinib and thoracic radiotherapy.
Authors: Yiyue Xu, Wenting Qie, Jinming Yu, Linlin Wang
Journal: Journal of Clinical Oncology (2022)

e20591 Background: Alectinib and thoracic radiotherapy (TRT) are important modalities in the management of ALK-rearranged non-small cell lung cancer. We therefore aimed to assess the incidence and risk factors of pneumonitis when these two treatments were combined. Methods: Patients with ALK-rearranged non-small cell lung cancer, receiving alectinib and TRT from January 2018 to December 2020 were reviewed, and the clinical and dosimetry data were collected. Logistic regression analyses were performed to evaluate risk factors associated with treatment-related pneumonitis (TRP). The prediction ability of dosimetry parameters for pneumonitis were examined by receiver-operating characteristic (ROC) curve analyses. Results: Of the 25 enrolled patients, 16 (64%) developed pneumonitis, and 12 (48%) developed grade 2 or higher pneumonitis. Logistics regression analyses revealed chemotherapy (OR = 8.750, 95% CI 1.207 - 63.428, p = 0.032), higher ipsilateral V5 (OR = 1.060, 95%CI 1.002 - 1.122, p = 0.043) and total lung V5 (OR = 1.083, 95%CI 1.000 - 1.174, p = 0.05) to be risk factors for TRP. Total lung V10, total lung V5, and ipsilateral V5 were strong predictors of TRP among the dosimetry parameters (AUC = 0.800, 0.786 and 0.781, respectively). After developing pneumonitis, 52% of patients recovered or improved, but one patient died due to respiratory failure. Conclusions: The combined use of alectinib and TRT significantly increased the risk of pneumonitis. Clinicians should consider the elevated risks and related dosimetric factors when deciding on combination treatment for ALK-rearranged NSCLC patients.
Estimating the impact of reducing the age of colorectal cancer screening on cancer incidence, mortality, and costs in Canada using OncoSim.
Authors: Anastasia Kalyta, Jonathan M. Loree, Mary A. De Vera, Stuart Peacock, Jennifer J. Telford, Carl J Brown, Fergal Donnellan, Sharlene Gill
Journal: Journal of Clinical Oncology (2022)

3526 Background: Organized colorectal cancer (CRC) screening programs currently cover Canadians aged ≥50 at average-risk of developing CRC and have contributed to declining CRC incidence. Rising incidence of early-onset CRC in individuals &lt; 50 has led to lowering of the recommended screening start age to 45 rather than 50 in some jurisdictions. We used OncoSim, a publicly-available simulation tool, to model the effects of earlier screening initiation on Canadian CRC incidence, mortality and healthcare costs. Methods: OncoSim uses Canadian population and cancer registry data to simulate a representative sample of individuals from birth to death. We modeled four scenarios: no screening in average-risk individuals, screening initiation at age 50, initiation age lowered to 45 in 2022, and initiation age lowered to 40 in 2022. Each includes 32 million simulated participants. In the model, average-risk screening involves biennial FIT, available to all simulated participants regardless of family history with participation of 60% at the first recruitment attempt and 80% for repeat screening. Participants with a family history in all 4 scenarios were eligible for additional screening by colonoscopy every 5 years. Results: In our model, earlier screening yields reduced CRC incidence and mortality with increasing benefit over time. By 2051, screening initiation at age 45 or 40 reduces age-standardized incidence by 3.4% and 4.8% respectively, and age-standardized mortality by 3.3% and 4.6% respectively, compared to initiation at age 50. Screening initiation at age 45 yields 3,848 additional quality-adjusted life-years (QALYs) in 2051 at a cost of $9,350 per QALY gained and a 5% increase in colonoscopies performed. Initiation at age 40 yields 6,255 additional QALYs at $16,350 per QALY gained and a 9% increase in colonoscopies. The difference in screening costs compared to screening from age 50 is consistent year-to-year after 2024. In 2051 screening costs increase by $75mil and $155mil per year with initiation at ages 45 and 40 respectively, while costs of cancer management (including diagnosis, treatment, recurrence, palliative and end of life care) decrease by $42mil and $57mil respectively. Conclusions: Our model predicts that lowering the CRC screening initiation age for average-risk Canadians to 45 or 40 could reduce CRC incidence and mortality. Costs per QALY gained are high in the first few decades but decrease over time. Costs are modest after 30 years of screening compared to other life-preserving interventions such as dialysis. Our results suggest that lowering the screening age in Canada may be warranted, but further investigation is needed to assess capacity for increased colonoscopy demand.
A multilevel intervention increased accrual of Native Hawaiians and other Pacific Islanders to a national breast cancer screening trial.
Authors: Srue Wakuk, Jeffrey L. Berenberg, Erin Capps, Paul Morris, Shirley Cheng, Kate Bryant-Greenwood, Kevin Cassel
Journal: Journal of Clinical Oncology (2022)

6547 Background: The University of Hawaii Cancer Center (UHCC) Minority/Underserved NCI Community Oncology Research Program (Hawaii MU NCORP) provides access to NCI-sponsored clinical trials in Hawaii. The Hawaii MU NCORP is dedicated to increasing minority and underserved accruals to clinical trials. Native Hawaiian women have the highest breast cancer incidence and mortality; only 26% of Micronesian women in Hawaii over the age of 40 have ever had a mammogram. In 2018, the Hawaii MU NCORP became a recruitment site for the ECOG-ACRIN Tomosynthesis Mammographic Imaging Screening Trial (TMIST). A pilot study was launched in 2019, to support our NCORP recruitment of underrepresented Native Hawaiian and other Pacific Islander (NHPI) women to the TMIST study. Subsequently, specific funding was provided by the NCI’s Center to Reduce Cancer Health Disparities that enabled the UHCC’s Office of Community Outreach and Engagement (COE) to develop an effective multilevel recruitment strategy together with the Hawaii MIU NCORP. Methods: To foster community awareness of the TMIST study among NHPI women, the UHCC COE hired a Community Health Educator (CHE). The CHE, a Pacific Islander woman, utilized small group educational sessions to provide culturally and linguistically appropriate cancer prevention information and promote the TMIST study to NHPI women in Hawaii. The CHE worked in partnership with Hawaii MU NCORP clinical research associates (CRAs) in these efforts. In 2020, statewide COVID-19 health and safety protocols were enacted, limiting public group interactions in Hawaii. Despite this challenge, the CHE successfully adapted the in-person educational sessions on clinical trials and TMIST to conduct sessions using Zoom and Facebook Messenger. Results: Before the hire of the CHE in 2019, only one Pacific Islander (Micronesian) woman was recruited to the TMIST in Hawaii. The CHE conducted 21 community health events with 426 attendees from 2019 to 2021. The Hawaii MU NCORP NHPI TMIST enrollment went from the 9.9% in 2018 to 2019, to 20.1% in 2019 to 2020 and to 33% in 2020 to 2021. To date, 18 Micronesian, 52 Native Hawaiian and 6 Other Pacific Islander women out of 353 participants ware enrolled. Conclusions: The multilevel intervention of our CHE, in collaboration with NCORP staff providing clinical trial awareness training and community outreach, resulted in increasing the enrollment of NHPI women to the TMIST Trial. CHE-led community health education sessions on cancer prevention can be delivered using emergent technologies and social media. The use of culturally and gender concordant CHEs working with CRAs have the potential to increase awareness and accruals to cancer clinical trials.
The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee
Authors: Elias Campo, Elaine S. Jaffe, James R. Cook, Leticia Quintanilla-Martinez, Steven H. Swerdlow, Kenneth C. Anderson, Pierre Brousset, Lorenzo Cerroni, Laurence de Leval, Stefan Dirnhofer, Ahmet Dogan, Andrew L. Feldman, Falko Fend, Jonathan W. Friedberg, Philippe Gaulard, Paolo Ghia, Steven M. Horwitz, Rebecca L. King, Gilles Salles, Jesus San-Miguel, John F. Seymour, Steven P. Treon, Julie M. Vose, Emanuele Zucca, Ranjana Advani, Stephen Ansell, Wing-Yan Au, Carlos Barrionuevo, Leif Bergsagel, Wing C. Chan, Jeffrey I. Cohen, Francesco d’Amore, Andrew Davies, Brunangelo Falini, Irene M. Ghobrial, John R. Goodlad, John G. Gribben, Eric D. Hsi, Brad S. Kahl, Won-Seog Kim, Shaji Kumar, Ann S. LaCasce, Camille Laurent, Georg Lenz, John P. Leonard, Michael P. Link, Armando Lopez-Guillermo, Maria Victoria Mateos, Elizabeth Macintyre, Ari M. Melnick, Franck Morschhauser, Shigeo Nakamura, Marina Narbaitz, Astrid Pavlovsky, Stefano A. Pileri, Miguel Piris, Barbara Pro, Vincent Rajkumar, Steven T. Rosen, Birgitta Sander, Laurie Sehn, Margaret A. Shipp, Sonali M. Smith, Louis M. Staudt, Catherine Thieblemont, Thomas Tousseyn, Wyndham H. Wilson, Tadashi Yoshino, Pier-Luigi Zinzani, Martin Dreyling, David W. Scott, Jane N. Winter, Andrew D. Zelenetz
Journal: Blood (2022)

Since the publication of the Revised European-American Classification of Lymphoid Neoplasms in 1994, subsequent updates of the classification of lymphoid neoplasms have been generated through iterative international efforts to achieve broad consensus among hematopathologists, geneticists, molecular scientists, and clinicians. Significant progress has recently been made in the characterization of malignancies of the immune system, with many new insights provided by genomic studies. They have led to this proposal. We have followed the same process that was successfully used for the third and fourth editions of the World Health Organization Classification of Hematologic Neoplasms. The definition, recommended studies, and criteria for the diagnosis of many entities have been extensively refined. Some categories considered provisional have now been upgraded to definite entities. Terminology for some diseases has been revised to adapt nomenclature to the current knowledge of their biology, but these modifications have been restricted to well-justified situations. Major findings from recent genomic studies have impacted the conceptual framework and diagnostic criteria for many disease entities. These changes will have an impact on optimal clinical management. The conclusions of this work are summarized in this report as the proposed International Consensus Classification of mature lymphoid, histiocytic, and dendritic cell tumors.
QOL-35. School reentry of children and adolescents with a brain tumor: can we improve family-school-hospital cooperation? An analysis of supportive and inhibiting factors as a result of a pilot project
Authors: Ulrike Leiss, Kerstin Krottendorfer, Thomas Pletschko, Andreas Peyrl, Amedeo Azizi, Karoline Wekerle, Fee Schneider, Verena Rosenmayr, Lisa Sanin, Liesa Josephine Weiler-Wichtl, Andrea Kutschera
Journal: Neuro-Oncology (2022)

Abstract OBJECTIVE: School reentry support focusing on providing information to schools and communication between patient/family-hospital-school is defined as a psychosocial standard of care in pediatric oncology (Thompson et al., 2015). This is critical for students with brain tumors (BT) - although it is not yet universally implemented - especially during follow-up, as they are a risk group for late effects. Due to long distances between family-hospital-school, limited personnel capacities and since 2020 Covid-19 restrictions, an online-event (OE) for teachers from external schools was designed, with the aim of: (1) strengthening cooperation, (2) breaking down barriers and (3) increasing level of knowledge. METHODS: 54 teachers participated in each of two OEs. Content was presented by an interdisciplinary team (clinician, clinical/neuropsychologist, social worker, teacher), followed by time for sharing experience. Two months after event 2, participants were asked to complete an evaluation in an anonymous online survey. Supportive and inhibiting factors for successful school reintegration were included in the survey and statistically analyzed. RESULTS: 54% of 23 respondents (70% teaching &amp;gt; 10 years) felt that their training before the event did not prepare them adequately for a teaching setting with seriously ill children (1-3 points on a 10-point Likert-scale). 92% rated their knowledge greater after the event. All interdisciplinary inputs were rated very useful and practical (79-88%: 8-10 points). 38% felt relieved to got to know contact persons. 33% rated teaching a student with BT as fundamentally challenging and felt more confident after the event. CONCLUSION: The results of this pilot project indicate that an online-information-event can increase knowledge and cooperation. Resulting promoting and inhibiting factors for school reintegration will be incorporated into future concept improvement. The findings further highlight the great importance of ongoing support in the form of a reintegration teacher and interdisciplinary input for schools to appropriately support students with BT.
Strategies for implementing an ePRO-based symptom management program (eSyM) across six cancer centers.
Authors: Michael J. Hassett, Christine Cronin, Nadine Jackson McCleary, Jessica J Bian, Sandra L. Wong, Hannah W. Hazard-Jenkins, Samira Dias, Julie Johnson, Deborah Schrag, Don S. Dizon, Raymond U. Osarogiagbon
Journal: Journal of Clinical Oncology (2022)

12017 Background: Electronic patient-reported outcome (ePRO)-based symptom management can improve cancer care outcomes. However, implementation is challenging as it requires 1) tremendous technical resources to integrate ePROs into the electronic health record (EHR), 2) substantial buy-in from clinicians and patients, 3) between visit symptom management, and 4) institutional investment to support engagement. Methods: The SIMPRO Consortium developed and deployed eSyM, an EHR-integrated ePRO-based symptom management program for medical oncology and surgery patients, at 6 cancer centers between September 2019-March 2022. Site teams document new and changes to implementation strategies monthly using REDCap (data collection is ongoing). Strategies are itemized using the Expert Recommendations for Implementation Change (ERIC) list and mapped to the Consolidated Framework for Implementation Research (CFIR) list of barriers. The SIMPRO Coordinating Center (Dana-Farber) reviews all ERIC-CFIR classifications for consistency. Results: To date, 162 distinct strategies have been documented. On average, sites have implemented 23 strategies, 5 preparing for go-live and 18 remaining active beyond go-live. Preparation of clinical staff, training, and routine program evaluation are consistent high impact strategies. Other adaptive strategies have varied across sites, including various approaches to patient and provider engagement. Foundational strategies have been deployed by the coordinating center to support the multi-center initiative. Conclusions: Methodical deployment using theory-based implementation strategies may foster adoption of novel health care delivery systems by patients, clinicians, and institutions. Attention to the specific high-value strategies identified by the SIMPRO Consortium could support similar ePRO deployment at other institutions. [Table: see text]
EPEN-17. Recurrent infratentorial ependymomas in children: a meta-analysis on molecular-based outcomes
Authors: Eric Montgomery, Vineeth Thirunavu, Nathan Shlobin, Sandi Lam, Michael DeCuypere
Journal: Neuro-Oncology (2022)

Abstract The overall prognosis of infratentorial ependymoma differs based on molecular signature, however the impact of recurrence on prognosis remains poorly defined in the pediatric population. PubMed, Scopus, Embase, and Ovid were searched for publications on recurrent infratentorial ependymomas in patients under 25 years of age. Exclusion criteria were case series of less than 5 patients and studies that did not provide individualized patient data. Our search yielded 472 unique articles, of which 17 were included in the analysis. There was a total of 460 recurrent ependymomas reported, with 52.8% WHO grade II tumors and 47.2% grade III. The overall mortality for recurrent infratentorial ependymoma was 49.1% (226/460). The pooled median survival was 32.39 months after recurrence (95% CI: 23.45-41.33). Gross total resection was achieved in 237 (53.1%) patients at initial presentation. Raw mean survival post-recurrence was 32.9 months (SD: 11.2 months) for those who received GTR for their primary tumor versus 23.7 months (SD: 10.8 months) for those who received subtotal resection (STR) (p &amp;lt; 0.001). There was no difference in survival between those that received GTR (49.3 months, 95% CI: 32.3-66.3) versus STR (41.4 months, 95% CI: 11.6-71.2) of their recurrent tumor (p=0.610). In the studies that provided molecular classification, there were 169 PFA tumors (83.3%) and 34 PFB (16.6%), with 28 that demonstrated 1q gain. PFA-A tumors demonstrated worse post-progression survival (24.7 months, 95% CI: 15.3-34.0) compared to PF-B (48.0 months, 95% CI: 32.8-63.2) (p=0.0073). The average post-recurrence survival for tumors with 1q gain was 5.93 months (SD: 9.15). The overall mortality rate for recurrent infrantentorial ependymomas was found to be 49.8%, with a pooled median survival of 32.39 months. Almost 90% of recurrent infratentorial ependymomas were of the PFA molecular subtype, and those tumors that demonstrated 1q gain had a worse survival than those that did not.